Primecuts – This Week In The Journals

January 30, 2012

By Robert Fakheri, MD

Faculty Peer Reviewed

This past week President Barack Obama delivered the State of the Union address. He comforted us that Osama bin Laden, much like Generalissimo Francisco Franco, is still dead. Meanwhile, the auto industry is well on its way to recovery and US exports are on the rise. Other comforting news are plans for reforms in the tax code that will simplify regulations and ensure fairness so that secretaries are not obliged to pay higher tax rates than their billionaire bosses. These headlines remind me that when treating our patients, comfort is an important issue. Medical interventions are often a balance between prolonging life and enjoying life. As healthcare providers, we should be mindful to avoid unnecessary or unproven restrictions on activities or diet, simplify patients’ medication regimens, and avoid unnecessary office visits and tests. And with that in mind, it’s time for this week’s Primecuts!

A recent article from JAMA [1] reports that exposure to marijuana was not associated with adverse effects on pulmonary function over 20 years, despite containing many of the same chemicals as tobacco. In fact, with low levels of exposure, pulmonary function measured by FEV1 and FVC were actually greater than baseline, with FEV1 increasing by 13 mL/joint-year (95% CI, 6.4 to 20; P < .001) and FVC by 20 mL/joint-year (95% CI, 12 to 27; P < .001). With higher exposure, these effects leveled off but remained at or above baseline. This non-linear association was attributed to short-term benefits from the inspiratory maneuvers (“toking”) that expand the lungs and strengthen muscles of the chest wall, eventually being counteracted by long-term damage from smoke exposure. It’s still unclear if marijuana smoke is less toxic than tobacco smoke, or if the observed results are secondary to the different habits of marijuana and tobacco users: 2-3 joints per month vs several cigarettes a day. As medical marijuana is slowly gaining acceptance (now legal in 16 states), more knowledge about its side-effect profile is certainly valuable. Although these data do not provide any evidence to encourage marijuana use, it does suggest that we should focus our cessation efforts on tobacco, given its well-established and far-reaching complications.

Moving from recreational activities to diet, a new study from Spain [2] found that in their population using mainly olive and sunflower oil, consumption of fried foods was not associated with coronary artery disease or mortality. Fried foods are often restricted because the frying process increases the fat content. Previous studies have shown an association with hypertension, obesity, dyslipidemias, and acute myocardial infarction, although several other studies have been negative. Information was obtained by a validated dietary questionnaire with 45-minute interviews to carefully identify the quantity and type of fried foods. Trying to explain the different observations from different studies, the authors hypothesized that multiple factors affect the nutritional content of fried foods, including the type of food, the frying technique (deep-fried or pan-fried), the type of oil, and the reuse of oils. Also, for some foods, beneficial effects may counteract the negative effects, such as production of natural ACE inhibitors from fried eggs. The results of this study suggest that fried foods with olive and sunflower oil may be safe alternatives, especially if they can help patients stay away from trans-fats, although it may require some cooking lessons and Spanish recipes. Further research could help tease out which oils and foods are preferred.

On the topic of lipids, a new study in Cell [3] found that p53 mutations in a breast cancer model exert their tumorigenic effect via the mevalonate pathway, also known as the pre-sterol phase of cholesterol synthesis that includes HMG-CoA reductase–the enzyme target of statin drugs. In their 3-dimensional culture model, p53 depletion enabled cells to revert from malignant morphology to normal acinar structure, demonstrating the vital role of p53 in this cell line. Gene expression analysis found significant upregulation of the mevalonate pathway. Inhibition of the pathway with simvastatin mimicked the effect of p53 depletion. These data were then translated to human subjects using blood samples from breast cancer patients and found a correlation between expression of p53 and expression of genes in the mevalonate pathway; clinically this was also associated with worse prognosis. The molecular biology goes a long way to explain the previously observed effects of statins in reducing the risk of breast cancers, particularly in estrogen- and progesterone-receptor negative (ER-/PR-) tumors, and also in treating these cancer subtypes. This correlates well with the basic science, since the majority of tumors with p53 mutations are ER-/PR-. Though more research must be done, statins may become an adjunctive therapy for these hormone-receptor negative breast cancers. I am sure patients would love to have their cancer and cholesterol treated by a single drug.

Even more convenient than killing two birds with one stone, how about managing your INR from the comfort of your own home instead of frequent visits to the office or clinic? A new meta-analysis from the Lancet [4] demonstrated that patients can safely manage their warfarin on their own and may even do better than medical professionals. The authors pooled individual data from 11 randomized trials for 6417 patients and 12,800 person-years of follow-up. Self-monitoring was associated with a significant reduction in thromboembolic events (hazard ratio 0.51; 95% CI 0.31–0.85), although no difference was found in bleeding or death. The decrease was even more striking in patients younger than 55 years (hazard ratio 0•33, 95% CI 0•17–0•66). The relevance of these data is brought into question by a commentary in the same issue citing the advent of newer drugs that do not require INR monitoring. However, in this age of cost-control, warfarin will likely remain a mainstay for oral anticoagulation. The cost of self-monitoring vs conventional management is still being debated, although the increase in productivity from fewer office visits seems like quite a boon. Although not all patients may be competent or responsible enough to manage their own warfarin, it is a reasonable option for many patients, and we should advocate for insurance companies to reimburse patients for point-of-care devices to measure INR at home.

Lastly, a provocative opinion piece from the Annals of Internal Medicine [5] promulgated a list of 37 scenarios of unnecessary testing, decided by unanimous approval from a panel of physicians. In light of increased pressure to reduce medical expenditures, the goal of the workgroup was to identify tests that were unlikely to be high-value in that they would not change management and/or the likelihood of a false positive would be greater than the likelihood of a true positive because of low pretest probability. The list could be simplified if some of the related items were grouped together. Nine items can be reduced to the following 4:

–Screening for colorectal cancer or prostate cancer in patients older than 75 years or with a life expectancy less than 10 years.

–Performing imaging studies in patients with non-specific low back pain

It will be interesting to see what happens with this list going forward. In the future, we may see insurance companies deny reimbursements if they find physicians ordering low-value tests. However, since most items have caveats that are open to clinicians’ judgment (eg, life expectancy), it may be difficult to pinpoint poor testing choices. By the same token, although many patients may be relieved by efforts to reduce testing and spending, there will remain the challenge of counseling certain patients who request testing that is not medically indicated.

To bring us back to the beginning and to close this week’s Prime Cuts, may God bless you and may God bless the United States of America.

Dr. Robert Fakheri is a 1st year resident at NYU Langone Medical Center

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